The present invention relates generally to improving the dispersibility of agglomerated hygroscopic powders such as pregelatinized starch, whole milk, skim milk, whole milk replacer, whey powders, powdered yeast and fish protein extracts, animal feeds, baby foods, and maltodextrines. More specifically, in its presently preferred form, the invention relates to methods for enhancing the dispersibility of agglomerated pregelatinized starch and to resulting compositions of easily dispersible agglomerated pregelatinized starch.
Mammals, including ruminants such as cattle and sheep and monogastric animals such as pigs, horses and human beings, often suffer from diarrhea or "scours". It has been reported that diarrhea is a serious health problem for adult cattle (U.S. Pat. No. 3,911,114) and causes high mortality rates for neonatal calves (U.S. Pat. No. 4,009,268). Monogastric animals, including pigs, horses and humans, are also reported to suffer significantly from diarrhea (U.S. Pat. No. 4,120,952), i.e., one-fifth of newborn pigs which contract diarrhea die without treatment (U.S. Pat. No. 4,010,262).
The above-mentioned patents disclose methods for treating diarrhea in the animal by administering oral dosages of an aqueous mixture of an antidiarrheal agent, pregelatinized starch (PGS). Typically the methods involve mixing a dry pregelatinized starch commercial product with water and forcing the resultant PGS solution or paste down a tube inserted in the animal's throat. (See, e.g., U.S. Pat. Nos. 3,911,114 and 4,010,262.) Other disclosed methods include mixing the pregelatinized starch with other liquids, such as milk, and feeding the mixture to the animal. (See, U.S. Pat. No. 4,120,952).
Although PGS appears to be an effective antidiarrheal agent, mixing pregelatinized starch with liquids is difficult due to the intrinsic properties of the starch. As produced commercially, pregelatinized starch is an extremely hygroscopic powder. Characteristic of hygroscopic powders, PGS disperses with difficulty in aqueous media. If added directly to such media too quickly and without sufficient agitation, the dry starch powder becomes encapsulated by stiff paste into balls of material which are very difficult to disperse. This incomplete dispersion makes the mixture more difficult to administer to the patient to the point that force-feeding may be required. Incomplete dispersion also means that a greater amount of pregelatinized starch may be required to achieve the desired antidiarrheic effect than if complete dispersal had been obtained.
The wettability of pregelatinized starch can be enhanced by agglomerating the particles of pregelatinized starch through controlled addition of water and redrying. The result is a coarse powder, agglomerated pregelatinized starch (APGS), that wets more readily in aqueous media and disperses more easily than pregelatinized starch. However, substantial care is still required when mixing agglomerated pregelatinized starch in water to avoid formation of lumps of stiff paste which resist dispersion.
In application of pregelatinized starch compositions such as PGS or APGS as an antidiarrheal, unskilled persons are expected to mix the compositions into water or aqueous suspensions and administer the solution orally to the patient. In intensive livestock production enterprises, however, instructions to take special precautions to mix medications slowly and carefully are often unheeded. To be accepted for routine use, a pregelatinized starch antidiarrheal product must be readily dispersible in aqueous media without the need for exceptional precautions for mixing, and with great margin for error. Thus formulations of pregelatinized starch compositions with mixing qualities superior to both PGS and APGS compositions presently available are required.
It is generally known in the art that the dispersibility of a composition can be improved through incorporation of a "dispersant" component which readily absorbs water. Many compounds are known to act as dispersants for certain compositions including raw starch used in tableting as an excipient and as a dispersant for PGS, and FDA approved anticaking agents for animal feeds such as polysorbate-60 and polysorbate-80. Sodium aluminum silicate may similarly be employed as an anticaking agent. U.S. Pat. No. 3,332,848 (Col. 1, line 68 to Col. 2, line 4) discloses incorporation of microcrystalline cellulose into multiple vitamin tablets to enhance the dispersibility of the tablets in aqueous vehicles. U.S. Pat. No. 3,696,637 discloses enhancing the dispersibility of estrogen in aqueous solutions by admixing microcrystalline cellulose with the hormone prior to mixing with water.
Although dispersants are generally known as a class, the choice of a dispersant is dependent primarily on the composition sought to be dispersed and the context within which the composition is intended to be used. In the present case, the dispersant must interact with a hygroscopic powder, APGS, intended to be ingested by livestock on a large-scale basis, and by human beings. It is therefore essential that the dispersant be non-toxic, inert and inexpensive. It is also preferred that the dispersant be a constituent of the normal diet of the patient. Further restrictions exist with respect to the nature and amount of dispersants that may be fed to livestock raised for human consumption, e.g., the U.S. Food & Drug Administration would be expected to require extensive retesting of PGS if the amount of dispersant in the antidiarrheal compositions were to exceed 10%. These and other regulatory restrictions would likely exist with respect to agglomerated hygroscopic powders such as milk, baby food, protein extracts and the like which are intended for direct human consumption.
As noted above, microcrystalline cellulose has been reported to function as a dispersant for estrogen in aqueous mixtures administered to cattle, (U.S. Pat. No. 3,639,637), and as a dispersant in vitamin tablets (U.S. Pat. No. 3,332,848). Microcrystalline cellulose is purified alpha cellulose particles prepared from processing alpha cellulose from fibrous plant materials. It is an inert, organic material and is a commercial product sold under various tradenames including Avical (American Viscose Division, FMC Corp.), as an excipient and extender in pharmaceutical tableting. (Avicel.RTM. Sales Brochure).
Although microcrystalline cellulose initially appears attractive as a possible dispersant for APGS, actual testing consistent with this suggestion has proven unsuccessful. As indicated in more detail below, applicant prepared mixtures of various proportions of microcrystalline cellulose and the antidiarrheal APGS starch. It was found that a minimum of 35% to 40% microcrystalline cellulose was required to significantly improve the dispersibility of APGS. The size of the microcrystalline cellulose particles was also found to influence dispersibility, the smaller sized particles (20 microns) being more effective than the larger 50 micron and 90 micron particles. At concentrations of about 35% microcrystalline cellulose, the cost of the mixture was three times that of APGS alone.
There continues to exist, therefore, a need in the art for a method of enhancing the dispersibility of agglomerated hygroscopic powders such as APGS and for easily dispersible APGS antidiarrheal compositions.